Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, KConFab investigators, Australian Ovarian Cancer Study Group

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.

METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.

RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).

CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Original languageEnglish (US)
Pages (from-to)R51
JournalBreast cancer research : BCR
Volume16
Issue number3
DOIs
StatePublished - May 26 2014

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Cytochrome P-450 CYP3A
Menarche
Case-Control Studies
Breast Neoplasms
Odds Ratio
Single Nucleotide Polymorphism
Estrone
Glucuronides
Homozygote
Risk Reduction Behavior
Heterozygote
Neoplasms
Alleles
Hormones

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, KConFab investigators, & Australian Ovarian Cancer Study Group (2014). Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study. Breast cancer research : BCR, 16(3), R51. https://doi.org/10.1186/bcr3662

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study. / GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network; KConFab investigators; Australian Ovarian Cancer Study Group.

In: Breast cancer research : BCR, Vol. 16, No. 3, 26.05.2014, p. R51.

Research output: Contribution to journalArticle

GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, KConFab investigators & Australian Ovarian Cancer Study Group 2014, 'Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study', Breast cancer research : BCR, vol. 16, no. 3, pp. R51. https://doi.org/10.1186/bcr3662
GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, KConFab investigators, Australian Ovarian Cancer Study Group. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study. Breast cancer research : BCR. 2014 May 26;16(3):R51. https://doi.org/10.1186/bcr3662
GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network ; KConFab investigators ; Australian Ovarian Cancer Study Group. / Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study. In: Breast cancer research : BCR. 2014 ; Vol. 16, No. 3. pp. R51.
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title = "Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study",
abstract = "INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95{\%} CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95{\%} CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95{\%} CI 0.75, 0.94; OR(hom) = 0.81, 95{\%} CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95{\%} CI 0.95, 1.19, OR(hom) = 1.07, 95{\%} CI 0.67, 1.72; P(trend) = 0.29).CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.",
author = "{GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network} and {KConFab investigators} and {Australian Ovarian Cancer Study Group} and Nichola Johnson and Frank Dudbridge and Nick Orr and Lorna Gibson and Jones, {Michael E.} and Schoemaker, {Minouk J.} and Folkerd, {Elizabeth J.} and Haynes, {Ben P.} and Hopper, {John L.} and Southey, {Melissa C.} and Dite, {Gillian S.} and Carmel Apicella and Schmidt, {Marjanka K.} and Annegien Broeks and {Van't Veer}, {Laura J.} and Femke Atsma and Kenneth Muir and Artitaya Lophatananon and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Ekici, {Arif B.} and Renner, {Stefan P.} and Elinor Sawyer and Ian Tomlinson and Michael Kerin and Nicola Miller and Barbara Burwinkel and Frederik Marme and Andreas Schneeweiss and Christof Sohn and Pascal Gu{\'e}nel and Therese Truong and Emilie Cordina and Florence Menegaux and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Henrik Flyger and Roger Milne and Zamora, {M. Pilar} and {Arias Perez}, {Jose Ignacio} and Javier Benitez and Leslie Bernstein and Hoda Anton-Culver and Argyrios Ziogas and {Clarke Dur}, Christina and Couch, {Fergus J} and Olson, {Janet E} and Sherman, {Mark E.} and Slager, {Susan L} and Vachon, {Celine M}",
year = "2014",
month = "5",
day = "26",
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pages = "R51",
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TY - JOUR

T1 - Genetic variation at CYP3A is associated with age at menarche and breast cancer risk

T2 - a case-control study

AU - GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network

AU - KConFab investigators

AU - Australian Ovarian Cancer Study Group

AU - Johnson, Nichola

AU - Dudbridge, Frank

AU - Orr, Nick

AU - Gibson, Lorna

AU - Jones, Michael E.

AU - Schoemaker, Minouk J.

AU - Folkerd, Elizabeth J.

AU - Haynes, Ben P.

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Dite, Gillian S.

AU - Apicella, Carmel

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Van't Veer, Laura J.

AU - Atsma, Femke

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Ekici, Arif B.

AU - Renner, Stefan P.

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael

AU - Miller, Nicola

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Guénel, Pascal

AU - Truong, Therese

AU - Cordina, Emilie

AU - Menegaux, Florence

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Flyger, Henrik

AU - Milne, Roger

AU - Zamora, M. Pilar

AU - Arias Perez, Jose Ignacio

AU - Benitez, Javier

AU - Bernstein, Leslie

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Clarke Dur, Christina

AU - Couch, Fergus J

AU - Olson, Janet E

AU - Sherman, Mark E.

AU - Slager, Susan L

AU - Vachon, Celine M

PY - 2014/5/26

Y1 - 2014/5/26

N2 - INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

AB - INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

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